Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes  

作　　者：TANG MeiKuen LEE Kenneth K 

机构地区：[1]Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University [2]Joint Laboratory for Regenerative Medicine, the Chinese University of Hong Kong-Jinan University [3]School of Biomedical Sciences,the Chinese University of Hong Kong [4]International Base of Collaboration for Science and Technology (JNU), the Ministry of Science and Technology & Guangdong Province [5]School of Biomedical Sciences, the Chinese University of Hong Kong

出　　处：《Chinese Science Bulletin》2011年第13期1361-1369,共9页

基　　金：supported by the National Natural Science Foundation of China (30770886,30570369,30340038,30973158);National High Technology Research and Development Program of China (2007AA02Z105);Natural Science Foundation of Guangdong Province (04105826);Key Science and Technology Program of Guangdong Province (2004B3-0601007);Key Science and Technology Program of Guangzhou (2006Z3-E5251);the Fundamental Research Funds for the Central Universities(21609408)

摘　　要：The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 （bmp-2） gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 （bmp-2 receptor） antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.

关 键 词：骨形态发生蛋白 肌腱细胞 愈合能力 迁移 扩散 BMP 表达模式 原位杂交 

分 类 号：R686[医药卫生—骨科学]